Signifcance HIV can be transmitted parentally and a vaccine capable blood-borne transmission of HIV sis desirable especially for intravenous drug users. Objective The purpose of this project is to use the SIV/rhesus macaque system to define the best imunization strategy to elicit protective systemic immune responses. Results The initial immunization protocol utilized soluble HIV-1 env antigens and for intramuscular immunization. The monkeys made very weak or no antibody responses to the soluble HIV-1 antigens. The animal were then immunized intramucularly with HIV-1 pseudovirions. Either a propietary adjuvant (polyphosphazene) or Alum was used for all the immunizations. All the animals made antibody responses after the initial pseudovirion immunization and were boosted 6 weeks PI with the same vaccine. The systemic and mucosal immune responses were moderate and the animals were challenged intravenously with a SIV/HIV chimeric virus (SHIV) . All the animals became infected after the challenge. Because the SHIV is non pathogenic and because we have prviously shown that infection with a nonpathogenic can protect rhesus macaques from challenge with a pathogenic SIV, these animals will be challenged vaginally with virulent SIV. All the animals successfully resisted the challenge virus. Future Directions The finding that vaccines can protect against vaginal challenge is highly significant and will be pursued to determine if this finding idicates that specila attempts to elicit ant-HIV mucosal immune responses are not needed. KEYWORDS HIV-1 pseudovirions, adjuvant, mucosal immunity, vaginal SIV challenge